EPITHELIAL TIGHT JUNCTION STRUCTURE IN THE JEJUNUM OF CHILDREN WITH ACUTE AND TREATED CELIAC SPRUE

Tight junction morphology was analyzed in freeze fracture electron mic rographs from biopsies at two locations along the surface-crypt axis i n the jejunum of children with treated and untreated sprue and in cont rol subjects. In control jejunum, strand number, meshwork depth, and t otal depth of the tight junction decreased from sui-face to crypt, con sistent with the concept of the crypt being more permeable than the su rface epithelium. In acute sprue, strand number was reduced in all reg ions along the surface-crypt axis, from 5.5 +/- 0.2 to 3.4 +/-: 0.3 (s urface) and from 4.7 +/- 0.2 to 3.6 +/-: 0.1 (crypt). Meshwork depth w as also reduced at all regions along the surface-crypt axis. Strand di scontinuities were more frequent in acute sprue. Aberrant strands appe ared below the main meshwork of crypt tight junctions in acute sprue. In asymptomatic children treated with the gluten-free diet, jejunal ti ght junctional structure only partially recovered. Strand number was r estored to normal at the surface, but was still decreased in the crypt s, from 4.7 +/- 0.2 to 3.9 +/- 0.3. We conclude that the epithelial ba rrier function of the small intestine is seriously disturbed by struct ural modifications of the tight junction in acute symptomatic celiac d isease, thereby accounting for increased ionic permeability noted in a parallel study on identical specimens. This epithelial barrier defect may contribute to diarrhea in celiac disease by a ''leak flux mechani sm.'' In children with sprue treated with a gluten-free diet, barrier dysfunction was only partly recovered, suggesting a level of ''minimal damage.''.